Ischemic Stroke in the Setting of Tuberculous Meningitis

The clinical syndrome of tuberculous (TB) meningitis leading to ischemic strokes is rarely seen today in immunocompetent adults native to North America. This entity is also notoriously difficult to diagnose because the presenting symptoms are often nonspecific. The authors describe a case of a man with TB meningitis which progressed to recurrent ischemic cerebral infarcts.     

A phase II study of sulofenur,a novel sulfonylurea,in recurrent epithelial ovarian cancer

Summary A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.     

Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

The plastic envelope method, a simplified technique for culture diagnosis of trichomoniasis.

Although culture of Trichomonas vaginalis is more sensitive than wet mounts in the diagnosis of trichomoniasis, the lack of convenience of culture prevents it from being widely used. To improve the acceptability of diagnosis by culture, a plastic envelope method (PEM) was devised. PEM permits both immediate examination and culture in one self-contained system. The medium consists of dry ingredients that are reconstituted with water before use. The effectiveness of immediate examinations by PEM was compared with that of wet mounts, and the effectiveness of culture by PEM was compared with that of culture in Trichomonas Medium No. 2 (Oxoid). Of 710 vaginal secretion specimens from symptomatic and asymptomatic women that were tested by the four methods, 62 (9%) were positive for T. vaginalis. The sensitivity was 66% by wet mount, 66% by immediate examination by PEM, 89% by cultures in Oxoid medium, and 97% by culture by PEM. The two culture methods had equivalent sensitivities but were significantly (P less than 0.0001) more sensitive than the two immediate methods. The combined immediate examination by PEM plus culture was more convenient to use than wet mounts plus culture in Oxoid medium. The long shelf-life of PEM's dry medium and its anticipated low cost are additional advantages.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Synovial sarcoma of abdominal wall: a case report and study of tumor fine structure

A case of synovial sarcoma in the abdominal wall of a 50-year-old Iraqi woman is reported. The ultrastructure of the tumor has been studied. Eight other cases of synovial sarcoma in the abdominal wall reported in the English literature up to 1978 have been reviewed. Synovial sarcomas in the abdominal wall tend to occur with a much greater frequency in women, whereas such tumors occurring in the extremities or the neck are more common in men than woman. No ultrastructural studies of abdominal wall synovial sarcomas could be found in the English literature. The ultrastructural characters of this tumor are similar to those of such tumors arising in the usual sites and the neck. However, the present study has indicated that the light and dark cells reported by earlier workers are not limited solely to the epitheloid areas but are also present in the spindle cell zones.     

高效液相色谱法测定小儿磨积片中橙皮苷的含量

目的:建立以高效液相色谱法测定小儿磨积片中橙皮苷含量的方法。方法:色谱柱为SpherisorbC18,流动相为甲醇-冰醋酸-水(25∶4∶71),检测波长为283nm,流速为2·0ml/min,柱温为50℃,灵敏度为0·16AUFS,进样量为20μl。结果:橙皮苷进样量在0·024μg~1·2μg范围内与峰面积积分值呈良好的线性关系(r=0·9999),平均回收率为99·1%(RSD=0·8%)。结论:本方法简便、快捷,灵敏度及准确度高,可为小儿磨积片质量控制提供依据。     

Allelopathic activity of the norharmane-producing cyanobacterium Synechocystis aquatilis against cyanobacteria and microalgae

The cyanobacterium Synechocystis aquatilis was observed growing as a monospecies in enriched phytoplankton samples in the laboratory, indicating its allelopathic activity on coexisting phytoplankton species. Therefore, the present study screened the culture medium of an axenic strain of this cyanobacterium for the presence of allelechemicals with algicidal properties by thin-layer chromatography (TLC). The allelopathic effect of S. aquatilis was evaluated by co-cultivation of target species of toxic cyanobacteria and green algae with this cyanobacterium, as well as by evaluation of norharmane (β-carboline 9H-pyrido(3,4-b) indole) crude extract prepared from the culture medium of Synechocystis. The growth of target algal species was measured as a cell density after 6 days incubation. The results showed that S. aquatilis produced the indole alkaloid norharmane with large quantities in the culture medium (86 μg l^?1). In co-cultivation experiments, S. aquatilis inhibited the growth of all tested cyanobacteria and green algae. Norharmane crude extract exhibited stronger inhibition of cyanobacteria (EC₅₀ = 4.6–4.8 μg ml^?1) than green algae (EC₅₀= 6.3–6.4 μg ml^?1) in a concentration-dependent manner, indicating its apparent role in the allelopathic activity of S. aquatilis. The possible applicability of the allelochemical, norharmane, as an algicide to prevent the formation of harmful algal bloom was discussed.